A Phase 2 interventional study of robatumumab in Osteosarcoma, Sarcoma, Ewing's and Peripheral Neuroectodermal Tumor, sponsored by Merck Sharp & Dohme LLC. Terminated. Open to participants aged 4 Years and older. Per ClinicalTrials.gov, last updated 2018-08-23.
Sponsored by Merck Sharp & Dohme LLC · Phase 2, Interventional, and Treatment
Participants with relapsed osteosarcoma that can be treated with surgery will be randomized to robatumumab administered intravenously (IV) at one of two dose levels. These participants will first receive robatumumab, have surgery performed, and continue to receive treatment every two weeks until a year of dosing, or until disease progression.
Participants with unresectable osteosarcoma or Ewing Sarcoma will receive robatumumab IV once every two weeks until disease progression. Participants who achieve a complete response (CR) or partial response (PR) after tumor evaluations may undergo surgical resection. After surgery, participants are eligible to receive 10 mg/kg robatumumab until disease recurrence/progression or one year of total dosing, whichever occurs first.
Participants with resectable osteosarcoma will be randomized to one of two dose levels of robatumumab to be given intravenously. These participants will first receive robatumumab according to randomized treatment, and have surgery performed 10 to 14 days after initial dosing. Participants will be allowed to recover from surgery four to six weeks prior to additional robatumumab administration at their randomized dose level. robatumumab will then be administered on the same calendar day once every two weeks. Participants will continue to receive robatumumab until disease recurrence, or until completing a year of dosing at the same dose level assigned, whichever occurs first.
Participants with unresectable osteosarcoma or Ewing Sarcoma will be assigned treatment to robatumumab IV administered once every two weeks and will continue to receive robatumumab until disease progression. Participants who achieve a CR or PR after tumor evaluations may undergo surgical resection. After surgery, participants are eligible to receive 10 mg/kg robatumumab until disease recurrence/progression or one year of total dosing, whichever occurs first.
A participant with either:
Exclusion Criteria:
Participants received robatumumab 0.3 mg/kg intravenously (IV) as a single dose on Day 1, followed by surgery on Day 10 to 14, and four weeks later, resumption of robatumumab 0.3 mg/kg on the same calendar day (± 3 days) once every 2 weeks until disease recurrence or up to 1 year of dosing. This group comprised participants with resectable osteosarcoma that relapsed within 6 months of prior definitive treatment (eg surgical metastasectomy) and having at least one prior chemotherapy regimen containing a platinum agent and doxorubicin.
Biological: robatumumab
Participants who received robatumumab 10 mg/kg IV as a single dose on Day 1, followed by surgery on Day 10 to 14, and four weeks later, resumption of robatumumab 10 mg/kg on the same calendar day (± 3 days) once every 2 weeks until disease recurrence or up to 1 year of dosing. This group comprised participants with resectable osteosarcoma that relapsed within 6 months of prior definitive treatment (eg surgical metastasectomy) and having at least one prior chemotherapy regimen containing a platinum agent and doxorubicin.
Biological: robatumumab
Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with relapsed and unresectable osteosarcoma refractory to prior chemotherapy with a platinum- and doxorubicin-containing regimen.
Biological: robatumumab
Participants received robatumumab 10 mg/kg IV biweekly until disease recurrence or up to 1 year of dosing. This group comprised participants with Ewing sarcoma refractory to prior treatment with at least 3 of the following agents: ifosfamide, etoposide, cyclophosphamide, doxorubicin, or vincristine.
Biological: robatumumab
Robatumumab IV every two weeks until disease progression.
Also known as: SCH 717454, SCH 717454 (19D12), MK-7454
Number of Participants Achieving a Complete Response or Partial Response (Group 3 Only)
This is a measure of the number of participants with a complete response (CR) or partial response (PR) to therapy, confirmed by central review. Response was based on Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) criteria.
Time frame: Up to 1 year following the start of study therapy
Number of Participants With >= 25% Change in Tumor Proliferation After Exposure to Robatumumab (Group 1 Only)
Tumor proliferation was measured using Ki-67 levels. Ki-67 is nuclear protein associated with cellular proliferation.
Time frame: Approximately 14 days
Number of Participants Achieving a Complete Response, a Partial Response, or Stable Disease (Group 2 Only)
Responses to treatment (complete response, partial response, or stable disease) confirmed by central review for Participants in Group 2. Response was based on Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) criteria.
Time frame: Up to 1 year following the start of study therapy
Overall Survival
This is a measure of the number of participants known to be alive at the time of data analysis for this study.
Time frame: From start of treatment until death or data analysis cut off (Up to 3.4 years)
Time Until Tumor Relapse (Group 1 Only)
This is a measure of the time from the start of the study to documented relapse of disease.
Time frame: From start of treatment until relapse or data analysis cut off (Up to 3.4 years)
Area Under the Concentration-time Curve (AUC) of Serum Levels of Robatumumab (Group 1 Only)
Time frame: End of infusion on Day 1, and then prior to surgery, before and after the 2nd, 3rd, and 8th doses (up to 20 weeks)
Incidence of Anti-robatumumab Antibodies
For biological agents, it is possible for the host (participant) to develop antibodies to the agent. This outcome measure was planned to find out the number of participants who developed the antibodies after treatment with robatumumab.
Time frame: Up to 2 years
Number of Participants Experiencing Treatment-Emergent Adverse Events
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. Treatment-emergent adverse events are those that occur after participants have received study treatment, or existing adverse events that occurred during screening that increase in severity after study treatment. Adverse events in the Group 1: 0.3 mg/kg arm that occurred after switching to the 10 mg/kg dose are displayed under the originally assigned treatment.
Time frame: Up to 2 years
Time to Disease Progression (Groups 2 and 3 Only)
This is a measure of the time from the start of the study to the time of documented disease progression.
Time frame: From the start of treatment until disease progression or data analysis cut off (Up to 3.4 years)
Overall Survival (Groups 2 and 3 Only)
This is a measure of the time of survival from first dose to documentation of death
Time frame: From start of treatment until death or data analysis cut off (Up to 3.4 years)
Duration of Response (Groups 2 and 3 Only)
This is a measure of the amount of time in which the tumor responded to therapy.
Time frame: From time of documented response until disease progression or data analysis cut off (Up to 3.4 years)
| Milestone | Group 1: 0.3 mg/kg | Group 1: 10 mg/kg | Group 2: 10 mg/kg | Group 3: 10 mg/kg |
|---|---|---|---|---|
| Started | 35 | 33 | 35 | 116 |
| Received treatment | 34 | 33 | 34 | 115 |
| Completed | 4 | 5 | 0 | 1 |
| Not completed | 31 | 28 | 35 | 115 |
| Withdrew: Treatment ongoing at data cut-off | 0 | 0 | 0 | 5 |
| Withdrew: Lack of efficacy | 23 | 26 | 30 | 97 |
| Withdrew: Lost to follow-up | 0 | 0 | 1 | 2 |
| Withdrew: Withdrawal by subject | 4 | 1 | 0 | 2 |
| Withdrew: Protocol violation | 2 | 1 | 0 | 0 |
| Withdrew: Adverse event | 1 | 0 | 3 | 8 |
| Withdrew: Not treated | 1 | 0 | 1 | 1 |
This is a measure of the number of participants with a complete response (CR) or partial response (PR) to therapy, confirmed by central review. Response was based on Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) criteria.
| Participants | Group 3: 10 mg/kg |
|---|---|
| Number of Participants Achieving a Complete Response or Partial Response (Group 3 Only) | 6 |
Tumor proliferation was measured using Ki-67 levels. Ki-67 is nuclear protein associated with cellular proliferation.
No measurements were reported for this outcome.
Responses to treatment (complete response, partial response, or stable disease) confirmed by central review for Participants in Group 2. Response was based on Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) criteria.
| Participants | Group 2: 10 mg/kg |
|---|---|
| Number of Participants Achieving a Complete Response, a Partial Response, or Stable Disease (Group 2 Only) | 6 |
This is a measure of the number of participants known to be alive at the time of data analysis for this study.
| Participants | Group 1: 0.3 mg/kg | Group 1: 10 mg/kg | Group 2: 10 mg/kg | Group 3: 10 mg/kg |
|---|---|---|---|---|
| Overall Survival | 17 | 16 | 7 | 28 |
This is a measure of the time from the start of the study to documented relapse of disease.
No measurements were reported for this outcome.
No measurements were reported for this outcome.
For biological agents, it is possible for the host (participant) to develop antibodies to the agent. This outcome measure was planned to find out the number of participants who developed the antibodies after treatment with robatumumab.
No measurements were reported for this outcome.
An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. Treatment-emergent adverse events are those that occur after participants have received study treatment, or existing adverse events that occurred during screening that increase in severity after study treatment. Adverse events in the Group 1: 0.3 mg/kg arm that occurred after switching to the 10 mg/kg dose are displayed under the originally assigned treatment.
| Participants | Group 1: 0.3 mg/kg | Group 1: 10 mg/kg | Group 2: 10 mg/kg | Group 3: 10 mg/kg |
|---|---|---|---|---|
| Number of Participants Experiencing Treatment-Emergent Adverse Events | 31 | 30 | 31 | 112 |
This is a measure of the time from the start of the study to the time of documented disease progression.
No measurements were reported for this outcome.
This is a measure of the time of survival from first dose to documentation of death
| Months | Group 2: 10 mg/kg | Group 3: 10 mg/kg |
|---|---|---|
| Overall Survival (Groups 2 and 3 Only) | 8.18 (2.96 to 10.58) | 6.93 (4.93 to 11.10) |
This is a measure of the amount of time in which the tumor responded to therapy.
No measurements were reported for this outcome.
Collected over Adverse events are reported from enrollment up to 5 weeks after the end of treatment (up to 2 years). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Group 1: 0.3mg/kg | — | 17/34 (50%) | 28/34 (82.4%) |
| Group 1: 10mg/kg | — | 8/33 (24.2%) | 30/33 (90.9%) |
| Group 2: 10mg/kg | — | 12/34 (35.3%) | 29/34 (85.3%) |
| Group 3: 10mg/kg | — | 57/115 (49.6%) | 104/115 (90.4%) |
| Event | Group 1: 0.3mg/kg | Group 1: 10mg/kg | Group 2: 10mg/kg | Group 3: 10mg/kg |
|---|---|---|---|---|
| PNEUMOTHORAXRespiratory, thoracic and mediastinal disorders | 4/34 | 1/33 | 0/34 | 1/115 |
| PAINGeneral disorders | 0/34 | 1/33 | 0/34 | 11/115 |
| RESPIRATORY FAILURERespiratory, thoracic and mediastinal disorders | 3/34 | 1/33 | 0/34 | 5/115 |
| PYREXIAGeneral disorders | 1/34 | 1/33 | 0/34 | 7/115 |
| FEBRILE NEUTROPENIABlood and lymphatic system disorders | 2/34 | 0/33 | 0/34 | 0/115 |
| DYSPNOEARespiratory, thoracic and mediastinal disorders | 0/34 | 0/33 | 2/34 | 3/115 |
| RESPIRATORY DISTRESSRespiratory, thoracic and mediastinal disorders | 0/34 | 0/33 | 0/34 | 6/115 |
| THROMBOCYTOPENIABlood and lymphatic system disorders | 0/34 | 0/33 | 1/34 | 4/115 |
| CHEST PAINGeneral disorders | 0/34 | 0/33 | 1/34 | 4/115 |
| CONSTIPATIONGastrointestinal disorders | 0/34 | 1/33 | 0/34 | 2/115 |
| Event | Group 1: 0.3mg/kg | Group 1: 10mg/kg | Group 2: 10mg/kg | Group 3: 10mg/kg |
|---|---|---|---|---|
| NAUSEAGastrointestinal disorders | 13/34 | 12/33 | 5/34 | 35/115 |
| PROCEDURAL PAINInjury, poisoning and procedural complications | 13/34 | 6/33 | 1/34 | 2/115 |
| PYREXIAGeneral disorders | 9/34 | 11/33 | 6/34 | 21/115 |
| CONSTIPATIONGastrointestinal disorders | 9/34 | 9/33 | 3/34 | 34/115 |
| COUGHRespiratory, thoracic and mediastinal disorders | 10/34 | 7/33 | 6/34 | 16/115 |
| VOMITINGGastrointestinal disorders | 9/34 | 8/33 | 3/34 | 25/115 |
| HEADACHENervous system disorders | 9/34 | 7/33 | 7/34 | 24/115 |
| DIARRHOEAGastrointestinal disorders | 3/34 | 6/33 | 2/34 | 29/115 |
| DECREASED APPETITEMetabolism and nutrition disorders | 5/34 | 4/33 | 4/34 | 27/115 |
| FATIGUEGeneral disorders | 7/34 | 7/33 | 7/34 | 23/115 |
Three participants did not receive study treatment but are included in the baseline population.
| Age, Continuous(Years) | Group 1: 0.3 mg/kg | Group 1: 10 mg/kg | Group 2: 10 mg/kg | Group 3: 10 mg/kg | Total |
|---|---|---|---|---|---|
| Mean | 23.7 ± 15.5 | 20.1 ± 10.3 | 27.5 ± 15.3 | 24.6 ± 11.4 | 24.3 ± 12.8 |
| Sex: Female, Male(Participants) | Group 1: 0.3 mg/kg | Group 1: 10 mg/kg | Group 2: 10 mg/kg | Group 3: 10 mg/kg | Total |
|---|---|---|---|---|---|
| Female | 14 | 13 | 11 | 43 | 81 |
| Male | 21 | 20 | 24 | 73 | 138 |
No study locations are listed for this record.
Plan to share: Yes — https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
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